Purpose: Pyridoxine-dependent epilepsy (PDE) is characterized by therapy-resistant seizures (TRS) responding to intravenous (IV) pyridoxine. PDE can be identified by increased urinary alpha-aminoadipic semialdehyde (α-AASA) concentrations and mutations in the ALDH7A1 (antiquitin) gene. Prompt recognition of PDE is important for treatment and prognosis of seizures. We aimed to determine whether immediate electroencephalography (EEG) alterations by pyridoxine-IV can identify PDE in neonates with TRS.
Methods: In 10 neonates with TRS, we compared online EEG alterations by pyridoxine-IV between PDE (n = 6) and non-PDE (n = 4). EEG segments were visually and digitally analyzed for average background amplitude and total power and relative power (background activity magnitude per frequency band and contribution of the frequency band to the spectrum).
Results: In 3 of 10 neonates with TRS (2 of 6 PDE and 1 of 4 non-PDE neonates), pyridoxine-IV caused flattening of the EEG amplitude and attenuation of epileptic activity. Quantitative EEG alterations by pyridoxine-IV consisted of (1) decreased central amplitude, p < 0.05 [PDE: median −30% (range −78% to −3%); non-PDE: −20% (range −45% to −12%)]; (2) unaltered relative power; (3) decreased total power, p < 0.05 [PDE: −31% (−77% to −1%); −27% (−73% to −13%); −35% (−56% to −8%) and non-PDE: −16% (−43% to −5%); −28% (−29% to −17%); −26% (−54% to −8%), in delta-, theta- and beta-frequency bands, respectively]; and (4) similar EEG responses in PDE and non-PDE.
Discussion: In neonates with TRS, pyridoxine-IV induces nonspecific EEG responses that neither identify nor exclude PDE. These data suggest that neonates with TRS should receive pyridoxine until PDE is fully excluded by metabolic and/or DNA analysis.